Unveiling the Time Course Mechanism of Bone Fracture Healing by Transcriptional Profiles.

Comb Chem High Throughput Screen

School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, China.

Published: March 2023

AI Article Synopsis

  • The study explores the complex process of bone fracture healing by examining gene expression changes over time in a rat model, highlighting four key healing stages.
  • Findings reveal specific pathways and genes that play crucial roles during different phases of healing, suggesting potential targets for future therapies.
  • The research provides valuable insights into potential molecular therapies that could enhance bone healing management in orthopedic care.

Article Abstract

Background: Bone fracture healing is a time-consuming and high-priority orthopedic problem worldwide.

Objective: Discovering the potential mechanism of bone healing at a time course and transcriptional level may better help manage bone fracture.

Methods: In this study, we analyze a time-course bone fracture healing transcriptional dataset in a rat model (GSE592, GSE594, and GSE1371) of Gene Expression Omnibus (GEO). RNA was obtained from female Sprague-Dawley rats with a femoral fracture at the initial time (day 3) as well as early (week 1), middle (week 2), and late (week 4) time periods, with nonfracture rats used as control. Gene Ontology (GO) functional analysis and pathway examinations were performed for further measurements of GSEA and hub genes.

Results: Results indicated that the four stages of bone fracture healing at the initial, early, middle, and late time periods represent the phases of hematoma formation, callus formation, callus molding, and mature lamellar bone formation, respectively. Extracellular organization was positively employed throughout the four stages. At the hematoma formation phase, the muscle contraction process was downregulated. Antibacterial peptide pathway was downregulated at all phases. The upregulation of Fn1 (initial, early, middle, and late time periods), Col3a1 (initial, early, and middle time periods), Col11a1 (initial and early time periods), Mmp9 (middle and late time periods), Mmp13 (early, middle, and late time periods) and the downregulation of RatNP-3b (initial, early, middle, and late time periods) were possible symbols for bone fracture healing and may be used as therapeutic targets.

Conclusion: These findings suggest some new potential pathways and genes in the process of bone fracture healing and further provide insights that can be used in targeted molecular therapy for bone fracture healing.

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Source
http://dx.doi.org/10.2174/1386207325666220412134311DOI Listing

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